【摘要】 目的探讨胆碱能受体M1、M2和M3亚型拮抗剂在改善大鼠失血性休克时微循环障碍中的不同作用。方法建立大鼠失血性休克模型。将大鼠随机分成5组:对照组、阿托品组、M1、M2及M3受体拮抗剂组。除对照组仅等量静脉补液(生理盐水和全血混合物3∶1)外,其余组动物在此基础上分别静脉注射非选择性M受体拮抗剂阿托品(1250mg/kg)、M1受体拮抗剂替仑西平盐酸盐水合物(telenzepine dihydrochloride hydrate)(0.22mg/kg)、M2受体拮抗剂西贝母碱(imperialine)(9.6×10-3mg/kg)或M3受体拮抗剂4-二苯乙酰氧-N-甲基哌啶甲碘化物(4-diphenylacetoxy-N-methylpiperidine methiodide,4-DAMP)(1.25×10-5mg/kg)。用微循环显微镜观察肠系膜微血管管径和血流形式的变化。每组选取25条三级微动脉进行统计(n=25)。结果阿托品或M1受体拮抗剂可使失血性休克大鼠的肠系膜微血管收缩明显减轻甚至扩张,微血管血流由粒流变为线粒流。M2或M3受体拮抗剂的上述作用不明显。结论选择性拮抗胆碱能M1受体可改善大鼠失血性休克时的微循环障碍。更多还原

【Abstract】 Objective To investigate the differential therapeutic effects of antagonists for muscarinic(M) receptor subtypes in hemorrhagic shock-induced microcirculatory dysfunction in the rat. Methods Rat hemorrhagic shock model was used in the study. Animals were randomly divided into 5 groups: control,atropine,M1 receptor(M1R) antagonist,M2R antagonist and M3R antagonist. On the basis of equivalent intravenous infusion of saline-blood(3∶ 1) mixture after shock,animals were intravenously infused with non-selective M receptor(MR) antagonist(atropine,1250mg/kg),M1R antagonist(telenzepine dihydrochloride hydrate,0. 22mg/kg),M2R antagonist(imperialine,9. 6 × 10-3mg/kg) or M3R antagonist(4-DAMP,1. 25 × 10-5mg/kg),respectively. Microscopy was used to measure blood flow patterns and changes of arteriole diameters in the mesenteric microcirculation. The diameters of 25 grade-3 arterioles(n = 25) were selected in each group for statistical analysis. Results Atropine and M1R antagonist telenzepine were significantly effective in improving the blood flow pattern(from particle flow to line-particle flow) and relaxing the arterioles. However,M2R or M3R antagonists were not effective in improving the microcirculatory dysfunction during shock. Conclusion Selective M1R blockade improves the microcirculatory dysfunction in rat hemorrhagic shock.更多还原